Neural Cell News Volume 11.34 | Aug 30 2017

TOP STORY

Fate Mapping of Human Glioblastoma Reveals an Invariant Stem Cell Hierarchy

The authors studied the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviors. Independent of an evolving mutational signature, they showed that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. [Nature] Abstract

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Differential HspBP1 Expression Accounts for the Greater Vulnerability of Neurons than Astrocytes to Misfolded Proteins

Investigators report that neurons and astrocytes showed markedly different activities in C terminus of Hsp70-interacting protein (CHIP), a cochaperone of Hsp70. In astrocytes, CHIP was more actively monoubiquitinated and bound to mutant huntingtin, the Huntington’s disease protein, more avidly, facilitating its K48-linked polyubiquitination and degradation. [Proc Natl Acad Sci USA] Abstract

A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity

The authors showed that the rate of fatty acid oxidation (FAO) regulates the activity of neural stem/progenitor cells (NSPCs). Quiescent NSPCs showed high levels of carnitine palmitoyltransferase 1a-dependent FAO, which was downregulated in proliferating NSPCs. [Cell Rep] Full Article | Graphical Abstract

Systemic Neutrophil Depletion Modulates the Migration and Fate of Transplanted Human Neural Stem Cells to Rescue Functional Repair

Delayed transplantation of central nervous system (CNS)-derived human neural stem cells (hCNS-SCns) at 9 or 30 days post-spinal cord injury (dpi) resulted in extensive donor cell migration, predominantly neuronal and oligodendrocytic donor cell differentiation, and functional locomotor improvements. Scientists report that acute transplantation of hCNS-SCns at 0 dpi resulted in localized astroglial differentiation of donor cells near the lesion epicenter, and failure to produce functional improvement in an all-female immunodeficient mouse model. [J Neurosci] Abstract

The Stem Cell Marker Lgr5 Defines a Subset of Post-Mitotic Neurons in the Olfactory Bulb

Using an Lgr5-EGFP reporter mouse line, scientists found that from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial and neuronal markers revealed that Lgr5 does not label stem cells in the OB, but instead labels a heterogeneous population of neurons with preference in certain subtypes. [J Neurosci] Abstract

Role of MEK Partner-1 in Cancer Stemness through MEK/ERK Pathway in Cancerous Neural Stem Cells, Expressing EGFRviii

Researchers utilized the EGFRviii mutation, which frequently occurs in brain cancers, to establish another cancerous neural stem cell line (F3.EGFRviii), and characterized its stemness under spheroid culture. The F3.EGFRviii cell line was highly tumorigenic in vitro and showed high ERK1/2 activity as well as expression of a variety of genes associated with cancer stemness, such as SOX2 and NANOG, under spheroid culture conditions. [Mol Cancer] Full Article

Osthole Promotes Endogenous Neural Stem Cell Proliferation and Improved Neurological Function through Notch Signaling Pathway in Mice Acute Mechanical Brain Injury

Investigators prepared a mouse model of cortical stab wound brain injury. Using the immunohistochemical and hematoxylin-eosin staining method, they demonstrated that osthole, a natural coumarin derivative, was capable of promoting the proliferation of endogenous neural stem cells and improving neuronal restoration. [Brain Behav Immun] Abstract

Arginine Deprivation Therapy: Putative Strategy to Eradicate Glioblastoma Cells by Radiosensitization

Arginine deprivation therapy (ADT) inhibited 2-D growth and cell cycle progression, and reduced growth recovery after completion of treatment in four different glioblastoma cell line models. Cells were less susceptible to ADT alone in the presence of citrulline and in a 3-D environment. Migration and 3-D invasion were not unfavorably affected. [Mol Cancer Ther] Abstract

Dual Roles of Aβ in Proliferative Processes in an Amyloidogenic Model of Alzheimer’s Disease

Scientists investigated the effect of Aβ on neuronal and glial proliferation by using an APP/PS1 transgenic model and in vitro assays. They showed that neurogenesis is affected early in the APP/PS1 hippocampus, as evidenced by a significant decrease in the proliferative activity due to a reduced number of both radial glia-like neural stem cells and intermediate progenitor cells. [Sci Rep] Full Article

Homophilic Binding of the Neural Cell Adhesion Molecule CHL1 Regulates Development of Ventral Midbrain Dopaminergic Pathways

Researchers mapped the temporal and spatial expression of cell adhesion molecule with homology to L1 (CHL1) and assessed functional roles of substrate-bound and soluble-forms of the protein during ventral midbrain (VM) dopaminergic (DA) development. Results showed early CHL1 in the VM, corresponding with roles in DA progenitor migration and differentiation. [Sci Rep] Full Article

Non-Canonical Soluble Amyloid-Beta Aggregates and Plaque Buffering: Controversies and Future Directions for Target Discovery in Alzheimer’s Disease

Scientists review some of the controversies regarding soluble Aβ aggregates and propose experiments designed to move forward towards new therapeutic approaches. [Alzheimers Res Ther] Full Article

AMPK Activation: Role in the Signaling Pathways of Neuroinflammation and Neurodegeneration

Researchers review recent literature on the pharmacological modulation of the adenosine monophosphate-activated protein kinase (AMPK) system as a potential molecular target in the management of neurodegenerative diseases. [Exp Neurol] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

AstraZeneca and Takeda Establish Collaboration to Develop and Commercialize MEDI1341 for Parkinson’s Disease

AstraZeneca and Takeda Pharmaceutical Company Limited announced that they have entered an agreement to jointly develop and commercialize MEDI1341, an alpha-synuclein antibody currently in development as a potential treatment for Parkinson’s disease. [AstraZeneca] Press Release

BERG Forms Research Collaboration with AstraZeneca to Identify New Therapeutic Targets to Treat Neurological Disorders Such as Parkinson’s Disease

BERG announced a research collaboration with AstraZeneca to identify and evaluate novel targets and therapeutics to treat neurological disorders such as Parkinson’s disease. [BERG] Press Release

NIH Renews BU ADC Award

The National Institutes of Health (NIH)/National Institute on Aging has awarded the Boston University Alzheimer’s Disease Center (BU ADC) a three-year, $5.4 million grant to continue research on ways to reduce the human and economic costs of Alzheimer’s disease through the advancement of knowledge. [Boston University School of Medicine] Press Release

Virginia Tech Researchers Win Alzheimer’s Research Awards from Virginia General Assembly

Three Virginia Tech researchers have each received money from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund, established to spur innovative investigations into Alzheimer’s disease and related disorders. [Virginia Polytechnic Institute and State University] Press Release

GeNeuro and Servier Announce Six-Month Results from CHANGE-MS Phase IIb Study in Multiple Sclerosis

GeNeuro and Servier announced six-month results from the twelve-month CHANGE-MS Phase IIb study of three doses of GNbAC1 for the treatment of patients with relapsing remitting MS. The data showed that GNbAC1 is well tolerated and that there is no statistical difference at six-months between GNbAC1 and placebo in the study’s primary endpoint of reducing the number of cerebral Gad-enhancing lesions as measured by MRI, nor on the other MRI measures of neuroinflammation. [GeNeuro] Press Release

Biogen Reports New Data from Phase Ib Study of Investigational Alzheimer’s Disease Treatment Aducanumab

Biogen announced results from a recently conducted analysis of the long-term extension of its ongoing Phase Ib study of aducanumab, the company’s investigational treatment for early Alzheimer’s disease. [Biogen] Press Release

Titan Pharmaceuticals Receives FDA Clearance to Begin Clinical Study of Parkinson’s Disease Treatment

Titan Pharmaceuticals, Inc. announced that the FDA has cleared the Investigational New Drug application for its ropinirole implant intended for treatment of the signs and symptoms of Parkinson’s disease. The Phase I/II clinical study in patients will commence shortly. [Titan Pharmaceuticals, Inc.] Press Release

European Commission Grants Approval for Mavenclad (Cladribine Tablets)

Merck KGaA, Darmstadt, Germany announced that the European Commission has granted marketing authorization for MAVENCLAD^® for the treatment of highly active relapsing MS in the 28 countries of the European Union in addition to Norway, Liechtenstein and Iceland. [Merck KGaA] Press Release

Adamas Announces FDA Approval of GOCOVRI^™ as First and Only Medication for the Treatment of Dyskinesia in Parkinson’s Disease Patients

Adamas Pharmaceuticals, Inc. announced that the FDA has approved GOCOVRI extended release capsules for treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. [Adamas Pharmaceuticals, Inc.] Press Release

Acorda Receives Refusal to File Letter from FDA for INBRIJA^™ (CVT-301, Levodopa Inhalation Powder) New Drug Application

Acorda Therapeutics, Inc. announced that it received a Refusal to File letter from the FDA regarding its New Drug Application (NDA) for INBRIJA. INBRIJA is an investigational treatment for symptoms of OFF periods in people with Parkinson’s disease taking a carbidopa/levodopa regimen. Upon its preliminary review, the FDA determined that the NDA was not sufficiently complete to permit a substantive review. [Acorda Therapeutics, Inc.] Press Release

Science Suffers as China’s Internet Censors Plug Holes in Great Firewall

China is tightening the screws on internet access, again. The latest crackdown—an evolving effort to ban virtual private networks not under government control—could seriously erode scientists’ ability to stay connected with peers abroad. [ScienceInsider] Editorial

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

In the last few days alone, the FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

FDA Warns US Stem Cell Clinic of Significant Deviations

The FDA posted a warning letter issued to US Stem Cell Clinic of Sunrise, Florida, and its Chief Scientific Officer Kristin Comella for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. [U.S. Food and Drug Administration] Editorial

NEW EACR-MRS: Seed and Soil: In Vivo Models of Metastasis
November 27-29, 2017
Berlin, Germany

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NEW Postdoctoral Positions – Cancer and/or Glioma Stem Cells (Cornell University)

Faculty Members – Neuroscience (Mercer University)

Lead Bioengineer – Parkinson’s Disease Research (Scaled Biolabs Inc.)

Research Associate – Parkinson’s Disease Research (Scaled Biolabs Inc.)

Research Associate – Neuroscience (Thomas Jefferson University)

Postdoctoral Position – Genetic and Viral Causes of Microencephaly (Duke University Medical Center)

Postdoctoral Fellow – Glioblastoma Multiforme (Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellow/Associate Positions – Neuroscience (State University of New York)

Postdoctoral Fellowship Positions and Principal Investigator – Brain Tumors (University of California, San Francisco)

Postdoctoral Researchers – Glial Cells (University of California, Davis)

Faculty Scientists – Neuroscience (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Neural Regeneration (Johns Hopkins University)

Postdoctoral Fellow – Stem Cell Biology and Neuroscience (University of Texas Health Science Center at Houston)

Postdoctoral Fellow Position – Alzheimer’s and Parkinson’s Diseases (Brigham and Women’s Hospital)

Biomedical Engineering Faculty Position – Neural Regeneration and Functional Tissue Engineering (Pennsylvania State University)

Postdoctoral Scientist – Neural Stem Cell Biology (Institute for Neuroscience of Montpellier)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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